Many antibodies get made in a surprising factory—animals.

The typical image of a modern biological research lab involves high-tech machinery and table-sized microscopes; at most, there might be some dishes of cells or a few mice floating around. For people with those images in mind, yesterday's odd report on how federal inspectors were surprised to find 841 goats at a California biotech facility they didn't even know existed might come as a surprise. Why, you might wonder, would Santa Cruz Biotechnology need a secret herd of goats at all?

As it turns out, goats (along with rabbits and a handful of other animals) play a key role in modern bioscience—but on the supply side, not the research side. A paper found in a major science journal might well have depended on a goat in some way; it's just that the lab never saw the animal. Instead, the goat probably lived at a facility like the one that's under investigation, while the research lab received the goat's contribution via a UPS shipment.

The men who stare at goats

So what does a goat (or a bunny) offer a biologist? Antibodies. Antibodies are useful for several procedures conducted by biologists because they can stick so specifically to a single target. If you can raise antibodies against a specific protein, you can then use those antibodies to purify that protein out of the huge mix of proteins produced by a cell. If you can generate antibodies to a protein that's on the surface of a cell, you can use them to purify whole cells out of a mixed population.

Antibodies can also be tagged with fluorescent molecules so that they light up all the locations within a cell where the protein normally resides. The result is images like the one below.

Antibodies, combined with fluorescent molecules, provide this image of a mixed cell population. But for each color involved, you need antibodies from a different species.

Now, you can generate antibodies using many different animals. All you need to do in many cases is inject the protein you're interested in—or even just a fragment of it—into the target animal; its immune system will do the rest. One convenient option is mice, since many research institutions have experience working with them, but mice have a short lifespan and a small blood supply, meaning you don't get much antibody out of them. (There are ways to create cells that provide a permanent supply of mouse antibodies, but they're technically challenging and have a few drawbacks.) If your mouse dies and you still need more antibody, your only option is to inject the protein into a new mouse and start over again, though with no guarantee that any of the new antibodies will have an equivalent quality to the old ones.

Researchers have instead turned to some larger and longer-lived species. Chickens can work well, since they pump lots of antibodies into their eggs, and they produce a lot of eggs. Rabbits live longer than mice, and it's possible to take larger blood samples from them. But goats are better still in both regards.

Euthanizing the factory

Even with goats, however, all good things must come to an end, and that's a problem for Santa Cruz Biotechnology. The company earns its money by providing a huge range of antibodies for all sorts of proteins, some of which are only going to be of interest only to a few dozen labs on the entire planet. For the company, the death of a goat can mean the end of a product.

And Santa Cruz isn't always given the chance to decide when the goats die. Research animals are covered by the Animal Welfare Act, enforced by the US Department of Agriculture. Its rules mean that, among other things, an animal suffering from problems that leave it in pain should be euthanized. But USDA inspectors have, in the past, found problems with Santa Cruz's compliance—including one goat with a large tumor that was kept alive to get more antibody out of it.

This doesn't mean that the recently discovered collection of 841 goats was intentionally hidden; the company told Nature that it had properly disclosed all goats, including the "secret" herd. But the USDA says it knew nothing about the goats and that the existence of the facility in question was directly denied by company officials, despite having been in use for over two years. Several of the goats found at the newly discovered facility were in poor health (though it's not clear any of them were at the point where regulations would require euthanasia).

Still, if you thought that there was no possible reason for a company to hide goats, Santa Cruz actually has one. Whether it did so or not will be determined by investigators.

51 Reader Comments

Tch! These USDA regulations are just another example of the nanny state mentality! Every year, legislators try to squeeze more bucks out of Small Biolab Owners whethers the regulations are necessary or not. I'm not even kidding!

Why do we have rules about these research animals when we are perfectly willing to kill and dissect animals for testing purposes all the time? Seems kind of silly to me. Not that I hate animals, but we should at least be consistent.

Why do we have rules about these research animals when we are perfectly willing to kill and dissect animals for testing purposes all the time? Seems kind of silly to me. Not that I hate animals, but we should at least be consistent.

There is a difference between deciding that for the purpose of research, "we're ok with killing an animal" and saying, "we don't give a shit what torturous existence you put an animal through".

The rules apply to research animals too. All animals used in the biotech industry are covered under IACUC (Institutional Animal Care and Use Committees). There's some bureaucracy associated with dealing with the FDA for the conduct of animal studies (GLP) and the USDA for the treatment of animals (AWA), but the industry has developed all kinds of methods to keep things straight.

It seems an unlikely thing to try and hide. "Quick Elmer, the Inspector is here, hide the 841 goats behind the bush over there!" I'm sure I've seen something like that on "Shaun the sheep".

On a slightly more serious note, a colleague of mine who was working in a lab studying anti-HIV vaccination told me that someone inadvertently needled themselves with a good whack of a gene therapy vector designed to induce a substantial immune response against the HIV gag protein. Apart from the visit to the hospital and the numerous health and safety forms they had to fill, they also became an excellent factory for human anti-HIV antibodies. A very useful resource for that lab. But not useful if they ever needed to have an HIV test, as they'd always test seropositive.

This is really cool. I never knew about the uses of antibodies, nor that animals are farmed for it almost like wool. I love science, and the enourmous applications of things that seem weird at first from a lay perspective.

A very useful resource for that lab. But not useful if they ever needed to have an HIV test, as they'd always test seropositive.

That's awesome and sucks.I got a TB vaccination years ago, so now I always test positive. Really don't want a chest x-ray every time I need a job health check. Thankfully that's not often.

Yeah what's up with that? When I moved to US back in '97 they said that I tested positive for TB. They gave me some meds for it, even though I submitted the paperwork that showed all my vaccinations including that I was vaccinated for TB. Doctor just looked at me like I was crazy. Now, I don't know much about vaccines and US policy on new comers but it would seem odd to do this. Everybody that I know from my country was given these meds, at least here in Chicago.

Why do we have rules about these research animals when we are perfectly willing to kill and dissect animals for testing purposes all the time? Seems kind of silly to me. Not that I hate animals, but we should at least be consistent.

I would like to second that the rules for research animals that are killed and dissected are quite strict, and taken very seriously. If your animal is going to experience pain, for example before euthanasia, you must give it anesthetics. If you do cancer research and your mice get tumors, you must sacrifice your mice before the tumors grow enough to cause the mice discomfort. And all use of animals must be pre-approved by an Institutional Review Board, from which research is routinely denied if you don't put enough care into fully describing everything, even if you are on the up and up. The image of scientists torturing animals for fun and profit is just not anywhere near reality.

Also Santa Cruz Biotech has often been in the news for, well, a 'lax' attitude with their animals. Occasionally you'll run into SCBiotech employees, and they'll sheepishly admit that sometimes even if they haven't produced an antibody in time, a vial will still get sent out and charged for, and you can tell that it's not exactly what they would do in that position, so management seems to be the problem. Santa Cruz locals are suspicious of Santa Cruz Biotech for their animal treatment, and the scientific community is suspicious of their products. Fortunately for the scientists, it's really easy to test an antibody to see if it works, and how specific it is. Unfortunately for the goats, inspectors only come around so often.

llama-lime: You sound like you are in the field maybe? A google image search on "animal testing" shows quite gruesome results. Are cosmetics testing done with the same care for animals? Are the pictures on google typical of a research facility?

A very useful resource for that lab. But not useful if they ever needed to have an HIV test, as they'd always test seropositive.

That's awesome and sucks.I got a TB vaccination years ago, so now I always test positive. Really don't want a chest x-ray every time I need a job health check. Thankfully that's not often.

Yeah what's up with that? When I moved to US back in '97 they said that I tested positive for TB. They gave me some meds for it, even though I submitted the paperwork that showed all my vaccinations including that I was vaccinated for TB. Doctor just looked at me like I was crazy. Now, I don't know much about vaccines and US policy on new comers but it would seem odd to do this. Everybody that I know from my country was given these meds, at least here in Chicago.

Beats me. When I was a lad (fifty years ago) childhood TB vaccination was routine in U.S. As when my parents were kids. For damned good reason. Articles like this always prompt me to link one of the finest chemists of all time, Paul Ehrlich, who used horse-drawn antibodies to fight the German diphtheria outbreak of 1895.

In desperate times, size matters.

Horses remained a draft standard for decades. When I was quite young my father took me to visit the equine serum facility at Penn. Veterinary School. There they had special padded upper rails on the horses' stall gate that an inoculated horse was trained to lean against to be bled. The height and shape were such that as the horse stood with lower neck against the pad, slight blood flow restriction caused the higher jugular and associated neck veins to swell a bit so they could be conveniently nicked with a scalpel and the blood collected in a beaker or flask.

I asked my dad if this hurt the horse at all. He replied not as far as anyone could tell, as the animals would routinely pony up to the bar and patiently stand and wait for the draw to complete for but a carrot as reward.

llama-lime: You sound like you are in the field maybe? A google image search on "animal testing" shows quite gruesome results. Are cosmetics testing done with the same care for animals? Are the pictures on google typical of a research facility?

I wouldn't use Google image search to make up your minds about anything. The chances are you will get 2 extremes with different agenda; 1) where testing animals floricking about in wide green pasture without a care in the world and 2) where testing animals are brutally tortured and killed for no reason.

I would think that reality would fall somewhere in the middle, or at least according to what I've seen in few pharma labs I've been to so far.

llama-lime: You sound like you are in the field maybe? A google image search on "animal testing" shows quite gruesome results. Are cosmetics testing done with the same care for animals? Are the pictures on google typical of a research facility?

I wouldn't use Google image search to make up your minds about anything. The chances are you will get 2 extremes with different agenda; 1) where testing animals floricking about in wide green pasture without a care in the world and 2) where testing animals are brutally tortured and killed for no reason.

I would think that reality would fall somewhere in the middle, or at least according to what I've seen in few pharma labs I've been to so far.

I've never seen a laboratory animal mistreated, but I've never been to a big pharma farm.

However, a lot of the images you're seeing are probably PETA-based propaganda, PETA being a front for various terrorist organizations. The reality is that by and large companies take this stuff fairly seriously, and pharma companies doubly so because they want to keep tighter controls on what exactly they're producing. You don't really want to be in violation of these guidelines because it can result in major disruptions to your business.

This is not to say it never happens, but its more likely that they'll keep animals alive who are in trouble rather than actually actively acting to harm the animals - after all, the animals are valuable.

Tch! These USDA regulations are just another example of the nanny state mentality! Every year, legislators try to squeeze more bucks out of Small Biolab Owners whethers the regulations are necessary or not. I'm not even kidding!

Why is this at -8? Is it because people don't get the puns, or because they do?

llama-lime: You sound like you are in the field maybe? A google image search on "animal testing" shows quite gruesome results. Are cosmetics testing done with the same care for animals? Are the pictures on google typical of a research facility?

I'm a computational biologist, so I'm only on the periphery, but a fraction of my (academic) colleagues work with mice, fruit flies, or nematodes, so I hear about their research, and know a small amount about the standards for research oversight. I've toured a few biotech animal facilities on the industrial side, and they appear to have differed primarily in scale (thousands of animals instead of dozens), and whenever you have such a larger scale, I would anticipate that it's easier for some animals to go unnoticed. And while my colleagues would often get attached to their animals, when their are thousands of them, the scientists will not have that opportunity. Most biologists, such as John Timmer, probably have more experience than I do.

I have a very low tolerance for gore, so I'm hesitant to look at google image search. I do know that there is a small subset of people who completely oppose all animal research, and a smaller subset of those who do not care about the actual facts since they already know what they know and any facts are just there to confuse them, and an even small subset of those people who firebomb my colleagues' homes for sins that have been imagined rather than actually committed. I have a feeling that any google image search will be dominated by those that are more interested in their cause than in the truth. Scientists who do work with animals will rarely speak up and set the record straight, as it makes them a target for violence, and while they may not mind putting themselves in danger, nobody wants to endanger their spouse or children. Usually the acts of violence are not reported in the press in order to avoid giving the terrorists any publicity. So there's an almost unnatural silence about it all, which is very odd for science.

These strict standards have evolved over time, and are in part due to activists, so animal rights activists must be given credit for improving the conditions of lab animals. They must also be given credit for exposing those who flaunt the rules in the current day such as Santa Cruz Biotech. However, barring the rare exceptions of gross misconduct, scientific research is less gruesome and causes less suffering to animals than, say, industrial farming of turkeys or cows. Having grown up in a rural area with industrial turkey farming, I can say with confidence that I'd much much rather be lab rat than a turkey that ends up on a Thanksgiving table.

Yeah what's up with that? When I moved to US back in '97 they said that I tested positive for TB. They gave me some meds for it, even though I submitted the paperwork that showed all my vaccinations including that I was vaccinated for TB. Doctor just looked at me like I was crazy. Now, I don't know much about vaccines and US policy on new comers but it would seem odd to do this. Everybody that I know from my country was given these meds, at least here in Chicago.

The TB vaccine isn't recommended for general use in the US, except for people who are likely to be exposed to it or otherwise likely to contract it somehow. I'm not entirely sure why, since supposedly the side effects are fairly minimal. I'm guessing the risk of infection in the US is considered too low (it is quite rare, 3.6 cases out of every 100,000 people in 2010), and that the always-positive test results could actually be a problem if they do get an TB infection (since the vaccine is not 100% effective).

I haven't ever really given research animals much thought, but I'm a little shocked there are rules like that since that kind of consideration isn't even given to people (who can communicate their pain and wishes) in similar condition. With such specific guidelines for animals, I would think it would be possible to create them for people who are suffering similarly and are seeking assistance.

I'd forgotten how kinky immunology is. Need something really sensitive? Get an antibody. Not sensitive enough. Get an anti-the-first-antibody-antibody and throw it in there. Maybe bind the new one to something.

Well, it's good to know that I got more out of that class than using α as short for "anti", which confuses the hell out of people trying to read my shorthand.

Interesting story, and while I hate the mistreatment of animals for any reason it seems to me that most scientists treat their animals well. Which only seems as it should be when, if you think about it, why would one want to jeopardize their career over something as stupid as not taking care of your livelihood.

Disclosure, I work in an immunology lab that performs animal research and antibody production (generally non-commercial for our own use) in the UK, but my comments and opinions are my own and not a reflection of my university or research group.

Quote:

(There are ways to create cells that provide a permanent supply of mouse antibodies, but they're technically challenging and have a few drawbacks.)

What??? Generally, monoclonal antibodies are superior in most applications (except possibly un-optimised Elisa assays etc) and certainly far more reproducible. They demand a far higher price than animal produced polyclonals and the fact that people are willing to pay that price should tell you something. They are not "technically challenging" either, its easy and well established technology (hell we do it in the lab because it's cheaper long term than buying them) it just takes a far bit of work so adds to the production cost.

llama-lime wrote:

These strict standards have evolved over time, and are in part due to activists, so animal rights activists must be given credit for improving the conditions of lab animals. They must also be given credit for exposing those who flaunt the rules in the current day such as Santa Cruz Biotech. However, barring the rare exceptions of gross misconduct, scientific research is less gruesome and causes less suffering to animals than, say, industrial farming of turkeys or cows. Having grown up in a rural area with industrial turkey farming, I can say with confidence that I'd much much rather be lab rat than a turkey that ends up on a Thanksgiving table.

But those standards also exist to ensure the scientific method, stressed animals have abnormal biochemistry & physiology (especially from the point of view of immunology). I would be highly dubious of the animal results from a lab with poor welfare standards, and their biological products may be affected too. Possibly explains the poor quality (non specific binding/ poor specific binding) of quite a few Santa Cruze antibodies we have bought in the lab...

I have to say coming from the UK (which has the highest scientific animal welfare standards in the world by far) the comments on here are amusing. The US regulation of animal welfare is a joke (barley adhered to bureaucratic paperwork). If Santa Cruze had been in the UK they would have potentially been shut down for this or those responsible criminally prosecuted.

baloroth wrote:

zlatanart wrote:

Yeah what's up with that? When I moved to US back in '97 they said that I tested positive for TB. They gave me some meds for it, even though I submitted the paperwork that showed all my vaccinations including that I was vaccinated for TB. Doctor just looked at me like I was crazy. Now, I don't know much about vaccines and US policy on new comers but it would seem odd to do this. Everybody that I know from my country was given these meds, at least here in Chicago.

The TB vaccine isn't recommended for general use in the US, except for people who are likely to be exposed to it or otherwise likely to contract it somehow. I'm not entirely sure why, since supposedly the side effects are fairly minimal. I'm guessing the risk of infection in the US is considered too low (it is quite rare, 3.6 cases out of every 100,000 people in 2010), and that the always-positive test results could actually be a problem if they do get an TB infection (since the vaccine is not 100% effective).

It doesn't work.... protects (if you get it at the right age) from childhood TB for a few years no real effect beyond that. Test results aren't really an issue since someone positive for TB will test far, far more +ve than a vaccinated individual, the problem is once you've test +ve and cleared it you will continue to test +ve so how do you know if you have caught it again (which is common)?

bsharp wrote:

I haven't ever really given research animals much thought, but I'm a little shocked there are rules like that since that kind of consideration isn't even given to people (who can communicate their pain and wishes) in similar condition. With such specific guidelines for animals, I would think it would be possible to create them for people who are suffering similarly and are seeking assistance.

But that is why there are rules. You don't KNOW if they are suffering, a mouse can't exactly say "You know, my right arse cheek is getting really sore from the 20+ injections you have given it could try the other side?" Also, when you "work" on people I hope it's done with their consent and for their benefit because otherwise I'll think you will find that that sort of thing is already very illegal.

TechGeek wrote:

Why do we have rules about these research animals when we are perfectly willing to kill and dissect animals for testing purposes all the time? Seems kind of silly to me. Not that I hate animals, but we should at least be consistent.

Sorry but there is a world of difference from killing something humanely and sticking needles in it day in day out often injecting irritating compounds designed to trigger an immune response that can lead to painful ulceration at the injection site. Animal drug testing is generally covered by the same or similar standards in most countries.

I don't mind gamma irradiated (your food is NOT made radioactive by it). But imagine if the goats have been vaccinated against human gut wall components? If any intact antibody got through from undercooked meat you would be shitting water for days...

Interesting story, and while I hate the mistreatment of animals for any reason it seems to me that most scientists treat their animals well. Which only seems as it should be when, if you think about it, why would one want to jeopardize their career over something as stupid as not taking care of your livelihood.

Hah! I work in a research lab, and we buy a lot of different antibodies. Santa Cruz are known for having one of the widest range of polyclonal (derived from the serum of immunized animals) antibodies - you can find almost anything in their extensive catalogue. But unusually, many of their polyclonals are goat Abs. Generally their rabbit Abs are pretty good, but given how utterly CRAP most of the goat polys have turned out to be in our hands, "SC goat poly" is a byword in our lab for "will most likely be a waste of time".

I have long cherished a theory that SC owned just a single goat, which I imagined frolicking in the California sunshine. And they sold us 1ml aliquots of bog-standard goat serum at $500 a pop.

I'm pleased to be proved wrong - 841 goats, eh? But most of their goat Abs are still crap.

If you were a US military dependent (son or daughter) you got vaccinations for TB, smallpox and a number of other unusual diseases as a matter of course administered in a military hospital in the 50's through 70's. Compliance was mandatory. Additional vaccinations would be made if you or your father were sent and then stationed overseas.

Hah! I work in a research lab, and we buy a lot of different antibodies. Santa Cruz are known for having one of the widest range of polyclonal (derived from the serum of immunized animals) antibodies - you can find almost anything in their extensive catalogue. But unusually, many of their polyclonals are goat Abs. Generally their rabbit Abs are pretty good, but given how utterly CRAP most of the goat polys have turned out to be in our hands, "SC goat poly" is a byword in our lab for "will most likely be a waste of time".

I have long cherished a theory that SC owned just a single goat, which I imagined frolicking in the California sunshine. And they sold us 1ml aliquots of bog-standard goat serum at $500 a pop.

I'm pleased to be proved wrong - 841 goats, eh? But most of their goat Abs are still crap.

On a slightly more serious note, a colleague of mine who was working in a lab studying anti-HIV vaccination told me that someone inadvertently needled themselves with a good whack of a gene therapy vector designed to induce a substantial immune response against the HIV gag protein. Apart from the visit to the hospital and the numerous health and safety forms they had to fill, they also became an excellent factory for human anti-HIV antibodies. A very useful resource for that lab. But not useful if they ever needed to have an HIV test, as they'd always test seropositive.

I cannot imagine the reaction of the lab safety compliance officer when told about the inadvertent needle.

Does your colleague put that on their resume? "Source for human anti-HIV antibodies." It is certainly a unique ... qualification?